Trial Outcomes & Findings for pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma (NCT NCT03655756)

Last Updated: 2022-08-08

Results Overview

Safety was reported using Common Terminology Criteria for Adverse Events (CTCAE) version 5.0. Feasibility was defined as the ability to treat at least five of the six patients enrolled without drug-related dose-limiting toxicity (DLT).

Recruitment status

COMPLETED

Study phase

EARLY_PHASE1

Target enrollment

7 participants

Primary outcome timeframe

28 ± 7 Days

Results posted on

2022-08-08

Participant Flow

This study had a goal of six evaluable patients. It was the intent of the study team to recruit an additional two patients to be screened and enrolled if any of the existing patients were lost to follow-up, withdrew consent, or exhibited disease progression.

Participant milestones

Participant milestones
Measure	IFx-Hu2.0 (Plasmid DNA) 0.1 mg/Lesion/Time Point Therapeutic Classification: * Noncellular, Therapeutic Cancer Vaccine \> Immunomodulator Route of Administration: * Intratumoral injection of cutaneous, subcutaneous or nodal lesions Mechanism of Action: * Injection of the IFx-Hu2.0 plasmid DNA construct into the target lesion facilitates the localized expression of the highly immunogenic Emm55 protein by the tumor cells on their cell surface. Physiological Effect: * This expression then primes a cascade of immune events that exposes the patient-specific abnormal tumor antigens to the effector mechanisms of the immune system. The immune response becomes systemic as inter-antigenic epitope spreading produces neoantigens to naïve T cells. Therefore, injected lesions are targeted along with non-injected lesions (abscopal effect). This is especially important in conditions where the mutational phenotype varies greatly among individual lesions. IFx-Hu2.0: Subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection).
Overall Study STARTED	7
Overall Study COMPLETED	6
Overall Study NOT COMPLETED	1

Reasons for withdrawal

Reasons for withdrawal
Measure	IFx-Hu2.0 (Plasmid DNA) 0.1 mg/Lesion/Time Point Therapeutic Classification: * Noncellular, Therapeutic Cancer Vaccine \> Immunomodulator Route of Administration: * Intratumoral injection of cutaneous, subcutaneous or nodal lesions Mechanism of Action: * Injection of the IFx-Hu2.0 plasmid DNA construct into the target lesion facilitates the localized expression of the highly immunogenic Emm55 protein by the tumor cells on their cell surface. Physiological Effect: * This expression then primes a cascade of immune events that exposes the patient-specific abnormal tumor antigens to the effector mechanisms of the immune system. The immune response becomes systemic as inter-antigenic epitope spreading produces neoantigens to naïve T cells. Therefore, injected lesions are targeted along with non-injected lesions (abscopal effect). This is especially important in conditions where the mutational phenotype varies greatly among individual lesions. IFx-Hu2.0: Subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection).
Overall Study Death	1

Baseline Characteristics

pDNA Intralesional Cancer Vaccine for Cutaneous Melanoma

Baseline characteristics by cohort

Baseline characteristics by cohort
Measure	IFx-Hu2.0 (Plasmid DNA) 0.1 mg/Lesion/Time Point n=7 Participants Therapeutic Classification: * Noncellular, Therapeutic Cancer Vaccine \> Immunomodulator Route of Administration: * Intratumoral injection of cutaneous, subcutaneous or nodal lesions Mechanism of Action: * Injection of the IFx-Hu2.0 plasmid DNA construct into the target lesion facilitates the localized expression of the highly immunogenic Emm55 protein by the tumor cells on their cell surface. Physiological Effect: * This expression then primes a cascade of immune events that exposes the patient-specific abnormal tumor antigens to the effector mechanisms of the immune system. The immune response becomes systemic as inter-antigenic epitope spreading produces neoantigens to naïve T cells. Therefore, injected lesions are targeted along with non-injected lesions (abscopal effect). This is especially important in conditions where the mutational phenotype varies greatly among individual lesions. IFx-Hu2.0: Subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection).
Age, Categorical <=18 years	0 Participants n=99 Participants
Age, Categorical Between 18 and 65 years	1 Participants n=99 Participants
Age, Categorical >=65 years	6 Participants n=99 Participants
Sex: Female, Male Female	3 Participants n=99 Participants
Sex: Female, Male Male	4 Participants n=99 Participants
Race (NIH/OMB) American Indian or Alaska Native	0 Participants n=99 Participants
Race (NIH/OMB) Asian	0 Participants n=99 Participants
Race (NIH/OMB) Native Hawaiian or Other Pacific Islander	0 Participants n=99 Participants
Race (NIH/OMB) Black or African American	0 Participants n=99 Participants
Race (NIH/OMB) White	7 Participants n=99 Participants
Race (NIH/OMB) More than one race	0 Participants n=99 Participants
Race (NIH/OMB) Unknown or Not Reported	0 Participants n=99 Participants
Region of Enrollment United States	7 participants n=99 Participants
AJCC Clinical Staging Stage III	1 Participants n=99 Participants
AJCC Clinical Staging Stage III C	4 Participants n=99 Participants
AJCC Clinical Staging Stage IV	2 Participants n=99 Participants

PRIMARY outcome

Timeframe: 28 ± 7 Days

Population: The data analysis is described to assess the safety of the injection of the study agent in six patients the intention-to-treat (ITT) approach will be used for response to treatment data analysis of this trial (secondary objective).

Outcome measures

Outcome measures
Measure	IFx-Hu2.0 (Plasmid DNA) 0.1 mg/Lesion/Time Point n=6 Participants Therapeutic Classification: * Noncellular, Therapeutic Cancer Vaccine \> Immunomodulator Route of Administration: * Intratumoral injection of cutaneous, subcutaneous or nodal lesions Mechanism of Action: * Injection of the IFx-Hu2.0 plasmid DNA construct into the target lesion facilitates the localized expression of the highly immunogenic Emm55 protein by the tumor cells on their cell surface. Physiological Effect: * This expression then primes a cascade of immune events that exposes the patient-specific abnormal tumor antigens to the effector mechanisms of the immune system. The immune response becomes systemic as inter-antigenic epitope spreading produces neoantigens to naïve T cells. Therefore, injected lesions are targeted along with non-injected lesions (abscopal effect). This is especially important in conditions where the mutational phenotype varies greatly among individual lesions. IFx-Hu2.0: Subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection).
Number of Participants With Serious Adverse Events (SAEs) and/or Dose Limiting Toxicities (DLTs) Serious Adverse Events (SAEs)	1 Participants
Number of Participants With Serious Adverse Events (SAEs) and/or Dose Limiting Toxicities (DLTs) Dose Limiting Toxicity (DLT)	0 Participants
Number of Participants With Serious Adverse Events (SAEs) and/or Dose Limiting Toxicities (DLTs) Participants Analyzed	6 Participants

SECONDARY outcome

Timeframe: 28 ± 7 days post treatment

Population: The intention-to-treat (ITT) approach will be used for response to treatment data analysis of this trial.

Evaluation of response rate and assessment of the antitumor immune responses induced by IFx-Hu2.0 per RECIST v1.1 for target lesions. Complete Response (CR), Disappearance of all target lesions. Partial Response (PR), ≥ 30% decrease in the sum of the longest diameters of target lesions compared with baseline. Stable Disease (SD), Neither sufficient shrinkage to qualify for partial or complete response (CR or PR) nor sufficient increase to qualify for progressive disease (PD). Progressive Disease (PD), Appearance of one or more new lesions and/or unequivocal progression of existing non-target lesions.

Outcome measures

Outcome measures
Measure	IFx-Hu2.0 (Plasmid DNA) 0.1 mg/Lesion/Time Point n=6 Participants Therapeutic Classification: * Noncellular, Therapeutic Cancer Vaccine \> Immunomodulator Route of Administration: * Intratumoral injection of cutaneous, subcutaneous or nodal lesions Mechanism of Action: * Injection of the IFx-Hu2.0 plasmid DNA construct into the target lesion facilitates the localized expression of the highly immunogenic Emm55 protein by the tumor cells on their cell surface. Physiological Effect: * This expression then primes a cascade of immune events that exposes the patient-specific abnormal tumor antigens to the effector mechanisms of the immune system. The immune response becomes systemic as inter-antigenic epitope spreading produces neoantigens to naïve T cells. Therefore, injected lesions are targeted along with non-injected lesions (abscopal effect). This is especially important in conditions where the mutational phenotype varies greatly among individual lesions. IFx-Hu2.0: Subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection).
Antitumor Response Induced by IFx-Hu2.0 Per RECIST v1.1 for Target Lesions. Complete Response (CR)	0 Participants
Antitumor Response Induced by IFx-Hu2.0 Per RECIST v1.1 for Target Lesions. Partial Response (PR)	1 Participants
Antitumor Response Induced by IFx-Hu2.0 Per RECIST v1.1 for Target Lesions. Stable Disease (SD)	2 Participants
Antitumor Response Induced by IFx-Hu2.0 Per RECIST v1.1 for Target Lesions. Progressive Disease (PD)	3 Participants

Adverse Events

IFx-Hu2.0 (Plasmid DNA) 0.1 mg/Lesion/Time Point

Serious events: 2 serious events

Other events: 7 other events

Deaths: 1 deaths

Serious adverse events

Serious adverse events
Measure	IFx-Hu2.0 (Plasmid DNA) 0.1 mg/Lesion/Time Point n=7 participants at risk Therapeutic Classification: * Noncellular, Therapeutic Cancer Vaccine \> Immunomodulator Route of Administration: * Intratumoral injection of cutaneous, subcutaneous or nodal lesions Mechanism of Action: * Injection of the IFx-Hu2.0 plasmid DNA construct into the target lesion facilitates the localized expression of the highly immunogenic Emm55 protein by the tumor cells on their cell surface. Physiological Effect: * This expression then primes a cascade of immune events that exposes the patient-specific abnormal tumor antigens to the effector mechanisms of the immune system. The immune response becomes systemic as inter-antigenic epitope spreading produces neoantigens to naïve T cells. Therefore, injected lesions are targeted along with non-injected lesions (abscopal effect). This is especially important in conditions where the mutational phenotype varies greatly among individual lesions. IFx-Hu2.0: Subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection).
Blood and lymphatic system disorders Clostridial sepsis	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
General disorders Multiple organ dysfunction syndrome	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Gastrointestinal disorders Pneumatosis	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.

Other adverse events

Other adverse events
Measure	IFx-Hu2.0 (Plasmid DNA) 0.1 mg/Lesion/Time Point n=7 participants at risk Therapeutic Classification: * Noncellular, Therapeutic Cancer Vaccine \> Immunomodulator Route of Administration: * Intratumoral injection of cutaneous, subcutaneous or nodal lesions Mechanism of Action: * Injection of the IFx-Hu2.0 plasmid DNA construct into the target lesion facilitates the localized expression of the highly immunogenic Emm55 protein by the tumor cells on their cell surface. Physiological Effect: * This expression then primes a cascade of immune events that exposes the patient-specific abnormal tumor antigens to the effector mechanisms of the immune system. The immune response becomes systemic as inter-antigenic epitope spreading produces neoantigens to naïve T cells. Therefore, injected lesions are targeted along with non-injected lesions (abscopal effect). This is especially important in conditions where the mutational phenotype varies greatly among individual lesions. IFx-Hu2.0: Subjects enrolled will receive a fixed IFx-Hu2.0 (plasmid DNA) dose of 0.1 mg injected in up to 3 lesions at a single time point (28-day follow-up post last injection).
General disorders Injection site reaction	71.4% 5/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor hemorrhage	28.6% 2/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Neoplasms benign, malignant and unspecified (incl cysts and polyps) Tumor pain	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Musculoskeletal and connective tissue disorders Back pain	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
General disorders Erythema	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Investigations Lymphocyte count decreased	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Skin and subcutaneous tissue disorders Pruritus	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Gastrointestinal disorders Constipation	28.6% 2/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Psychiatric disorders Insomnia	28.6% 2/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Vascular disorders Hypertension	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Gastrointestinal disorders Diverticulitis	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Metabolism and nutrition disorders Anorexia	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Gastrointestinal disorders Dry mouth	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
General disorders Fatigue	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Gastrointestinal disorders Flatulence	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Vascular disorders Lymphedema	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.
Musculoskeletal and connective tissue disorders Muscle spasms	14.3% 1/7 • Day 0 to 28 days ± 7 business days from the last dose administered.

Additional Information

James Bianco, MD - Chief Executive Officer

Morphogenesis, Inc

Phone: 8138756600

Email: [email protected]

Results disclosure agreements

Principal investigator is a sponsor employee Moffitt shall be free to publish any academic articles, presentations, or abstracts of the Study results (including supporting data); provided that any such manuscript is first submitted to Company thirty (30) days prior to the proposed publication date so that Company may take any action necessary to protect its confidential information and intellectual property rights prior to said publication.
Publication restrictions are in place

Restriction type: OTHER